Fiducial marker for oncological and other procedures

ABSTRACT

A method and apparatus for marking a target with a radiopaque marker is disclosed. The method may include providing a radiopaque filament and inserting at least portion of the radiopaque filament into tissue. The filament may extend continuously and at last partially around a perimeter of the target so that the filament is disposed in a plurality of surgical planes to demarcate the target with the radiopaque maker.

CLAIM OF PRIORITY

The present application is a non-provisional of, and claims the benefitof U.S. Provisional Patent Application Nos. 62/805,595 filed Feb. 14,2019, and 62/943,464 filed Dec. 4, 2019; the entire contents of each isincorporated herein by reference.

CROSS-REFERENCE TO RELATED PATENT DOCUMENTS

This patent application is also related to U.S. patent application Ser.No. 16/160,229 filed on Oct. 15, 2018; the entire contents areincorporated herein by reference.

BACKGROUND

After certain surgical procedures, patients often require radiationtherapy to irradiate any remaining diseased or damaged tissue such ascancer cells or excessively dividing cells near the site of surgery.This radiation therapy occurs after abnormal tissue is removed and thesurgical cavity is closed. Markers may be used to help delineate wherethe removed abnormal tissue was to aid the physician in directing theradiation therapy.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, which are not necessarily drawn to scale, like numeralsmay describe similar components in different views. Like numerals havingdifferent letter suffixes may represent different instances of similarcomponents. The drawings illustrate generally, by way of example, butnot by way of limitation, various embodiments discussed in the presentdocument.

FIG. 1A illustrates a left cranio-caudal radiographic view of atraditional radiopaque marker in tissue.

FIG. 1B illustrates a left mediolateral oblique radiographic view of atraditional radiopaque marker in tissue.

FIG. 2 illustrates imaging artifacts generated by markers in aradiograph of tissue.

FIG. 3 illustrates a radiopaque marker in a tissue cavity.

FIG. 4 illustrates an example of a radiopaque marker pattern.

FIGS. 5A-5B illustrate different perspective views of a tumor bed cavitymarked by a radiopaque filament.

FIG. 6 shows an example radiopaque marker pattern.

FIG. 7 shows another example radiopaque marker pattern.

FIG. 8 shows another example radiopaque marker pattern.

FIG. 9 shows another example radiopaque marker pattern.

FIG. 10 shows another example radiopaque marker pattern.

FIG. 11 shows another example radiopaque marker pattern.

FIG. 12 shows another example radiopaque marker pattern.

FIG. 13 shows another example radiopaque marker pattern.

FIG. 14 shows another example radiopaque marker pattern.

FIG. 15 shows another example radiopaque marker pattern.

FIG. 16 shows another example radiopaque marker pattern.

FIG. 17 shows another example radiopaque marker pattern.

FIG. 18 shows an example of a radiopaque marker.

FIG. 19 shows an example of another radiopaque marker.

FIG. 20 illustrates an example of an anchor on a radiopaque marker.

DETAILED DESCRIPTION

After certain surgical procedures, patients may require radiationtherapy to irradiate any remaining cancer cells or excessively dividingcells near the site of surgery. This radiation therapy occurs afterabnormal tissue is removed and the surgical cavity is closed. However,after the cavity is closed, it is extremely difficult for a radiationoncologist to gauge the actual extent of the original tumor and thesubsequent tumor bed especially when there is a complex closure of theincision. This manipulation of tissue is typically referred to as tissuere-arrangement where a portion of the closure moves in various planes ina non-symmetric closure. This is particularly common in soft tissuesurgical procedures. Since radiation target/treatment planning istypically performed using x-ray based imaging after the soft tissue hasbeen closed, the imaging often does not delineate the precise locationwhere malignant or otherwise diseased tissue was removed and whenradiation therapy to the tumor bed may be required. If radiationtreatment is not necessary, it still may be beneficial to mark thesurgical cavity for future monitoring and follow up of the patient.

Inaccurate representation of the tumor bed causes uncertainty, thusleading to less precise targeting/administration of radiation to theexact area of interest and potential irradiation of healthy tissue. As aresult, benign tissues unnecessarily receive an increased dose ofradiation therapy, the area of radiation treatment can be unnecessarilylarge, and the tumor bed can receive too little radiation therapy. Aneed therefore exists to more effectively mark the original tumor bed toallow the radiation oncologist to easily and precisely visualize theextent of the original tumor bed cavity.

After some surgeries, a post-operative fluid filled pocket can form thatthis is referred to as a seroma. A seroma is a pocket of fluid thattypically forms after an injury, most commonly after a surgicalprocedure in the area where tissue was removed such as a tumor. Seromasare filled with serous fluid which may be a pale yellow, transparentfluid that contains protein, but no blood cells. Seromas areparticularly common after breast surgery. While they are common,surgeons and patients prefer to avoid this complication.

Currently, various methods are used by radiation oncologists to attemptto radiographically identify the tumor bed cavity. The most commonmethods include visualizing a seroma that may form within the tumor bedand visualizing surgical clips or metallic fiducials (“seeds”) which maybe placed along the tumor bed.

A seroma may or may not be present, may represent only part of the tumorbed, or may involve an area much larger than the tumor with inclusion ofthe entire surgical cavity (e.g., if the incision was much larger thanthe actual tumor). Therefore, the seroma might not represent the truetumor bed size and location, and the seroma might lead a radiationoncologist to inaccurately plan the radiation treatment location andsize. As a result, healthy and/or benign tissue may be irradiatedunnecessarily, and cancer cells remaining in the tumor bed can be missedby the radiation therapy. In addition, numerous clinical papers haverepeatedly proven that the size of seroma changes over time. Since mostradiation treatments occur many weeks following surgery, a highprobability exists that the size of the seroma may not clearly identifythe actual tumor bed.

Vascular clips, that are typically used for hemostasis applications arecommonly used to mark the cavity. With surgical clips or seeds, thesurgeon places these markers in the tumor bed during or after excisionof the tumor. They can be placed anywhere with a goal to identify themargins where surgical planes are defined as superior (towards thehead), inferior (towards the feet), medial (towards the center), lateral(towards the side), anterior (towards the front), and posterior (towardsthe back). However, the fundamental issue with clips or seeds is thatthey only define a single point and not a plane. Thus, many clips orseeds are placed to provide true plane definition. Numerous clinicalpapers state that a minimum of 4-5 clips need to be placed in order toprovide some certainty of the cavity definition. Numerous clinicalpapers also report that clips or seeds can migrate relativelyfrequently. Since they are small, attaching them to tissue is notguaranteed and when the tissue is manipulated, the clips or seeds candetach and then simply “float” in the seroma cavity.

FIGS. 1A-1B illustrate the use of a commercially available rigid,absorbable frame which includes integrated radiopaque markers thatattempts to address the migration problem. The marker 102 is a rigid,absorbable radiolucent frame with several embedded titanium radiopaquemarkers.

FIG. 1A is a left cranial-caudal (LCC) view and FIG. 1B is a leftmediolateral-oblique (LMLO) view. The frame keeps the markers frommoving around. The challenge with this configuration is that the frameis rigid and palpable therefore the patient can feel it under the skin.Additionally, the individual markers which are titanium still do notaddress plane delineation and margin definition since there are a smallnumber of markers and when imaged with a magnetic resonance imaging(MRI), ultrasound, x-ray or computerized tomography (CT), the metalmarkers may exhibit imaging related artifacts as shown in FIG. 2. Thesesingle point reference components potentially contribute to inaccuracyin target delineation for radiation therapy. The device may not alwaysbe adaptable to various sizes of tumor cavities. In certain situationsits use may be restricted to relatively small cavities with a regular,basic geometric configuration.

Therefore, a need for a marker for applications such as breastlumpectomy (breast conserving surgery) exists, and the marker may beinert, implantable, durable, non-absorbable, comfortable, holds positionafter surgical manipulation, and radiopaque (under any imaging modalityincluding but not limited to x-ray, mammogram, CT, ultrasound, MRI,etc.) without causing excessive imaging artifact. It may be desirablefor the marker to be attached, for example threaded or otherwise securedto tissue along the entire cavity length and conform to the shape of themargin. It would eliminate artifacts, reduce or eliminate palpability,and would allow the surgeon to properly perform current era surgeriessuch as breast oncoplastic lumpectomy where any remaining empty void isfilled by the surgeon after the tumor tissue is taken out. This is notlimited to just breast surgery and other types of soft tissue procedurescan benefit, such as lung, pancreas, prostate, liver, and otherprocedures. This is accomplished by manipulation of portions of breasttissue using re-arrangement techniques to completely close the surgicalcavity without leaving a gap where a seroma can form and minimizes anyskin dimpling. By attaching the elongated, continuous, radiopaque markeralong the various cavity planes such as by threading the marker intissue or clipping the marker to tissue, regardless of surgicaltechnique employed, the radiation oncologist is be able to easilyvisualize postoperatively the 3-dimensional extent of the tumor bed.Visualization of the marker improves the accuracy of treatment planningfor radiation therapy applied to the tumor bed. During the subsequentradiation therapy, the marker's 3-dimensional outline of the tumor bedmay be easily observed during the setup for treatment. During the actualtreatment, visualization of the marker's outline of the tumor bed canoccur even when the bed/target is moving as a result of patient movementdue to, for example, the patient's breathing, heartbeat, bowel motionetc. Based on this imaging, the delivery of radiation therapy istherefore adapted in real-time to the motion to ensure that theradiation is precisely and accurately delivered to the target tissue.Having the continuous, multi-plane marker can also allow the radiationoncologist to simply trace the marker as a planned target and use it asthe boundary for radiation as opposed to drawing a larger, symmetricoutline around the clips. This would dramatically reduce the toxicradiation dosage to the patient.

An example of a marker that applies to any of the markers disclosedherein and is promising includes an elongated, flexible, continuousradiopaque adaptable tissue marker as illustrated in any of FIGS. 3-19of the present application. The marker can be formed into a filamentwith or without an attached needle that can be threaded through orotherwise attached to tissue. Since the marker is continuous andflexible it can be deployed/attached/threaded into a symmetric ornon-symmetric shape area and/or volume. This area or volume can then beeasily correlated to the radiotherapy treatment plan that closelymatches the area and/or volume shape. Unlike single point markers, theradiation oncologist has to estimate the treatment plan and create orextrapolate a shape that encompasses the point markers observed. Otherdevices can be used to deliver the filament to the tissue, such asneedle drivers, or automatic suturing devices such as suture passers.This can be done with one, single filament or multiple filamentsegments. The filament can be self-knotted to itself andsecured/anchored to tissue or it can have features that prevent itselffrom slipping out of position. Features such as barbs for example oreven coatings can be applied to the marker if a knotless system isdesired. One can attach crimped absorbable or non-absorbable componentsinstead of using knots to limit the filament from migrating after it hasbeen threaded through tissue. Whether temperature-affected ormoisture-activated for example, a coating can create a feature thatprevents the marker from migrating. The marker may be extruded or coatedwith hydrogel or similar material. When hydrogel comes into contact withmoisture it expands. This is an example where a hydrogel coating can beapplied to a flexible marker to prevent unwanted movement of the markerthat may be used with any of the marker examples disclosed herein. Also,mechanical clips can be used to attach the filament to the tissue.Coatings can also be applied to enhance visualization under specificimaging modalities such as ultrasound and MRI. Thus, a marker may bevisible only under x-ray for example and a coating could be applied tothe marker to make the marker visible under MRI or ultrasound. Thecoating does not have to be continuous, so it may just show segments ofthe continuous marker under one type of modality, for example MRI and inits entirety under x-ray or CT.

Other optical indicators may be added to any of the radiopaque markersdisclosed herein to help a surgeon or other physician visually observethe marker. For example, the marker may be colored to allow it to beeasily visualized (e.g. adding a blue color to the filament). Similarly,other coatings or indicators may be included with the radiopaque markersso that the operator may visualize and distinguish and contrast themarker from adjacent tissue.

It also may be desirable to have a marker that is only visible underx-ray or CT for example and not under MRI. Thus, there is an advantageto only having the marker visible with selective imaging modalities.

The marker can also be a paint or a gel for example that can be applied,coated or otherwise or painted onto a surface. For example, adhesive canbe made to have radiopaque particles and as the adhesive is applied toone or more surfaces, the radiopaque particles will highlight the path.Again, the path will be continuous over an area.

In another example the marker can be sprayed on. The radiopaqueparticles can cover the entire tumor bed for example. However, over timefor example certain particles can be absorbed and disappear and certainparticles remain forever. Thus, any example may provide complete volumecoverage for radiation planning and then disappear to provide an outlineor minimal radiopaque marking that minimizes obstruction of the targettreatment area during follow up imaging such as mammography. Theradiopaque particles can range in shape between 0.01 microns and 500microns. They can be encapsulated in various forms, such as glass.Various materials can be used such as silanated barium glass, silanatedglass ceramic, Ba—Al—B silicate glass, SiO2, and others.

The marker can be embedded, attached or even painted onto an absorbableor non-absorbable structure such as a mesh, dermal matrix or a compliantballoon. The structure has to be transparent to radiological imaging, sothe adjacent surgical planes are easily seen through the structure. So,a minimal amount of radiopaque material is visible under imaging. Insome situations, no more than 10 mm wide in the shortest axis of theradiopaque marker can obstruct imaging (be radiopaque).

The filament can have various diameters. The diameters can range, forexample, between 0.1 mm and 0.3 mm. Larger filaments can be developedand have diameters larger than 0.4 mm, or 1 mm or 10 mm with round orother cross-sections such as oval, square, rectangular, elliptical, etc.The tensile strength of the filament can have a range between 5 and 20Newtons. The elongation can be greater than 50% with weight % of theradiopaque material to be between 20-40%. In addition, the elongation ofthe filament can be greater than 50%. The radiopaque filament can bemade from various materials including polymer. The filament may remainpermanently in the body, or it may be fabricated from a bioresorbablematerial. There are various ways to make the filament radiopaque, suchas with barium sulfate, BaSO₄. The markers can also have metallicmaterial or nanocrystals. As mentioned earlier, various coatings can beapplied to the filament to increase friction to prevent movement. It isalso feasible that various types of filament can be created with variousradiopaque patterns. For example, one can imagine where a filamentappears radiographically like closely spaced dots, short lines, or acontinuous line. This way for example, as seen later, the surgeon canmark specific surgical planes such as posterior/lateral orlateral/superior with a uniquely identifiable marker. There is anadvantage of having a continuous, flexible radiopaque marker, unlikediscrete clips which have no special relationship. Also, unlike discreteclips, the continuous marker will be attached to itself and identifies aplurality of surgical planes compared to a single marker that can onlyidentify a single point on a single plane.

If the flexible filament is extruded or drawn for example, it may haveradiopaque segmental markers 1802 separated by non-radiopaque gaps 1804,as seen in FIG. 18 thereby forming a filament 1806 of any desiredlength. The marker may remain flexible to allow manipulation such asallowing formatting of a knot. The ends of each adjacent radiopaquesegments will have fixed and non-adjustable separation. In any exampleit may be desirable that the gap between segments to be equal to or lessthan the length of each radiopaque marker segment. It may be desirablethat the length of the gaps is kept minimal so that at least oneradiopaque segment can be associated with a single surgical plane. Theradiopaque frequency of segments could be high enough so when imaged forexample they will blend together. In another example, the patternfrequency of radiopaque marker bands may be different for differentmarkers. So, one can chose for example a dotted marker to be placed onthe medial/posterior/lateral surfaces and segmented marker could beplaced along superior/posterior/inferior surfaces. So, two differenttypes of marker filaments could be deployed to distinguish the planes.The cross-sectional diameter of the radiopaque portion can be the samesize as the non-radiopaque portion.

FIG. 19 shows an example of a marker where the shortest filament 1906can consist of one flexible radiopaque marker 1902 and onenon-radiopaque segment (FIG. 19). It should be noted that the flexibleradiopaque marker has enough flexibility to be able to tie into at leastone knot.

The elongated marker is adaptable to placement in all organ systems in avariety of patterns and techniques. Use of the marker is thus notlimited to breast surgery. Applications are found in every area of thebody where tumors are removed leaving a tumor bed. Tumors requiredelineation for targeting treatment, whether primary, nodal, or ametastatic tumor site even if a resection is not feasible, or physicianscan benefit from postoperative visual guidance to direct postoperativetherapy to residual malignant or non-malignant disease. Examples includetreating a keloid, non-invasive breast cancer, or heterotopicossification of a joint.

Sites beyond the breast include but are not limited to the lung, colon,rectum, bladder, prostate, esophagus, brain, head & neck, muscle, skin,vasculature, and all other areas of potential disease. For example, aphysician can mark the location where vessels and nerves are connectedto provide future imaging targets for radiation therapy. The marker canbe used to outline the location of where a radical prostatectomy, lymphnode dissection, sarcoma resection, or head & neck surgery withreconstruction has occurred, especially since for tumor bed sites suchas these, postoperative radiation therapy is routinely required to treatresidual disease in the operative bed. The marker can be used toidentify a bronchial anastomosis, esophagogastric, or the colorectalanastomosis at risk for a local recurrence after resection of anintervening tumor. Importantly, none of these sites after surgery isaccurately visualized radiographically without a marker. As a result,radiation therapy cannot be accurately planned or precisely delivered,surrounding normal tissues receive unnecessary radiation dose, and thetarget region can receive too little dose.

In general terms the continuous radiopaque filament may extend withinone or more adjacent planes and/or between adjacent planes. The filamentcan start on any of the planes by attachment method such as by suturing,clipping, or other means. The filament may extend parallel to thestarting plane until an adjacent plane is reached. Then when theadjacent plane is reached, the filament may turn in a differentdirection along the adjacent plane, being attached again in a parallelfashion to that plane. This can continue on some or every adjacent planeas the filament reaches it and turns.

A number of examples of markers are disclosed herein.

FIG. 3 shows an example of a marker 302. The marker 302 is threaded fromthe bottom (posterior) of the cavity 304 up to the top (anterior) of thecavity 304 in one or multiple continuous paths across a plurality ofsurgical planes that are stacked on top of one another and substantiallyparallel to one another or may even cross. The marker is threadedcontinuously and follows the contours of the cavity, extendingcontinuously partially or completely around the perimeter of the cavity,optionally forming a spiral or helix around the cavity. In FIG. 3, allthe planes are defined as the filament completely surrounds the cavity.The sections of the filament are shown on the inside of the cavity withgaps in between, however in those gaps, the filament is stillcontinuous, but since it is sutured into the tissue, the filament is notobservable by the naked eye but will show up on a radiograph as acontinuous filament.

FIG. 3 shows the filament extending from the bottom of the cavity to thetop of the cavity, but this may also be reversed from top (anterior) tobottom (posterior). It may be desirable to make sure that all the sidesof the cavity are threaded from the deepest point to the highest. Whatmay also be desirable is to only mark the portion of the cavity wherethe tumor was located. So, if the tumor was only at the lower portion ofthe surgical cavity, only that portion of the cavity would be marked andthus the upper portion or anterior portion would remain unmarked. Thus,the marker may form a continuous band in a spiral or helix in aplurality of planes in the posterior portion of the cavity and theanterior portion of the cavity may remain marker-free. In this exampleone can see the filament is a running thread, weaving in and out oftissue where segments of the filament are disposed on the inner surfaceof the cavity and other segments are unexposed and disposed in thetissue walls surrounding the cavity. It may be desirable that onesurrounds the bottom portion of the tumor bed first. A small portion ofthe filament tail end may be left to protrude out of the tissue andwhile the remainder of the filament proceeds around the posterior-most(or anterior-most plane). Once the loop defining the posterior plane iscompleted and the filament tail is reached, the filament and thefilament tail may be knotted together. Alternatively, a knot may beformed in the suture filament end that anchors that end in tissuewithout requiring knotting with another portion of the filament andprevents movement of the filament. The filament may then proceed upward(or downward if you started at the anterior plane) with a runningfilament in a spiral pattern. The tied-off loop or knot will secure thefilament at the starting end of the cavity and it will not move as it isthreaded upward. A single knot or multiple knots can be self-knotted atany location around the marker depending on the tissue type to eliminateslippage of the knot and filament so the marker is firmly anchored inplace. Once the filament reaches the desired height or position, thefilament is tied off with another knot or knots to secure it at theopposite end, in this example the top of the cavity assuming thefilament started at the bottom of the cavity. The posterior knot 306 andanterior knot 306 are shown in FIG. 3. The same result may be obtainedby suturing in shorter segments instead of a continuous spiral wherethere are breaks or even multiple discrete rings may be used. However,still having a continuous flexible filament adjacent to plurality ofplanes. It is also feasible that instead of having knots to tie off theloops, the filament can be attached via clips or other techniques thatrely increasing friction between the filament and the tissue to reducemovement such as those disclosed herein. It is assumed that instead ofbottom to top, the user may choose to create a path from side to side,(example lateral to medial) or in any other preferred orientation ordirection.

The following figures illustrate perspective diagrams showing thefilament pattern described above in FIG. 3. These figures only showcube-like openings so that the six surgical planes are easilydiscernable. One of skill in the art will appreciate that surgicalcavities are not limited to square/rectangular cavities and any cavityshape is possible, including and not limited to oval, round andasymmetric shapes, deformed volumes and non-geometric shapes. Also, thestarting points are suggested as examples. The starting point in alldiagrams and ending point can be on any of the planes that areconvenient for the surgeon. The following figures are merely examples.

FIG. 4 shows a surgical cavity 402 idealized as a square cavity wherefor the sake of simplicity, the bottom of the cavity is the posteriorplane and the top of the box as anterior plane. The side walls representlateral, medial, superior and inferior surgical planes where the lateraland medial planes are opposed to another and the inferior and superiorplanes are also opposed to one another. Therefore, the bottom plane istissue as well as the four side wall planes. The top, or anterior planis an open surgical incision. Filament 404 which may be any of theradiopaque markers disclosed herein starts 406 at the bottom of thecavity, which in this example is the posterior plane. A small filamenttail extends out of the tissue and then is sutured in and out of theposterior tissue plane. Once the loop comes around back to the startingpoint, is tied off 410 with the tail (the knots going forward may bedepicted by a circle) 410. The suture continuously extends from thestarting point around all four walls and therefore continuously extendsacross the four vertical surgical planes (lateral, medial, inferior,superior) in short linear segments that may lie in a single horizontalplane that is in the posterior plane, parallel to the posterior plane,or transverse to the posterior plane, although this is not required andthe suture may be sutured continuously or discontinuously around thefour walls with each segment along a wall in a different plane. Once theknot is tied off, the filament turns upward toward the top of theanterior plane and proceeds in a circumferential path around the fourwalls of the cavity upward in the cavity anteriorly into the next planeforming another looped marker around the perimeter and then again upinto the next plane and so on until the desired height is reached andthen the end 408 is tied off 412 again with an adjacent portion of thefilament. As mentioned, earlier, this spiral can be achieved with acontinuous filament or with shorter discrete segments and additionalknots. A continuous filament is a desirable pattern because it limitsthe number of knots, but it can also be achieved with shorter segmentsand more knots. In this example the segments of the radiopaque markerare linear along a wall and coupled together with a corner connectorfilament that joints the filament in two adjacent planes which forms aplurality of loops (square, rectangular, circular, or other shape) thatare stacked on top of one another. The loops may be canted relative tothe one another, parallel to one another or a combination of canted andparallel.

Thus, in FIG. 4, the continuous filament continuously extends betweenmultiple vertical and horizontal planes and may have linear sectionsconnected with connectors such as right-angle sections. The spiral orhelical pattern is formed by the filament continuously extending aroundthe perimeter from bottom to top of the surgical cavity and through allfour walls surrounding the surgical cavity. FIG. 4 shows the suturecontinuously sutured to tissue in the cavity but one of skill in the artwill appreciate that the suture may be sutured into and out of thetissue and therefore portions of the suture may in fact be hidden fromview since the suture is under tissue, although under an x-ray thefilament would show up as a continuous line.

FIGS. 5A-5B show an actual 3-D imaging model derived from a CT basedreconstruction of what the filaments would like from FIG. 4. FIG. 5Ashows a slightly different perspective of the same 3-D reconstructedmodel, thus showing very clearly the shape of the tumor bed cavity fromdifferent perspectives. The tumor bed is surrounded or encompassed bythe marker 404. The entire width and height are clearly depicted. Eachplane, anterior, posterior, lateral, medial, superior and inferior areclearly delineated. This is a reconstructed image of multiple CT planesdemonstrating the marker laid out in a spiral configuration.

FIG. 6 shows another technique for contouring the cavity 602. This maybe accomplished with a single 604 or multiple filaments which may be anyof the radiopaque markers disclosed herein. Here the single filamentmarker outlines the bottom posterior tissue surface and then the sides(superior, inferior, lateral and medial) thereby identifying multipleplanes that are transverse to one another and in some situationsorthogonal to one another. The filament starts 606 with a first bite onone of the walls in one vertical plane, leaving a small filament tail,then threads the filament down the wall in a substantially linear pathalong the vertical plane as indicated by the arrow, then turns in atransverse or approximately orthogonal direction once it reaches or isadjacent the bottom of the cavity in the posterior plane. The filamentthen runs across the posterior surface in a substantially linear pathacross the posterior plane and then changes direction transversely upthe opposite wall in a substantially linear path that is substantiallyparallel to the first downward path and in a vertical plane that may besubstantially parallel to the first vertical plane. Once the desiredheight is reached, the filament turns transversely (may be orthogonally)from the linear path just taken to follow a short horizontal linear pathin the same vertical plane that the filament followed up, then bendstransversely into an adjacent wall of the cavity into different verticalplane for a short horizontal distance until it again turns downward toextend along a linear path downward to the bottom of the cavity in theposterior plane. The filament turns again into the bottom posteriorplane crossing itself until it reaches the opposite wall where thefilament turns upward and extends upward along the wall in this fourthvertical plane. The filament finally turns horizontally in the fourthvertical plane, extends a short horizontal distance and then wrapsaround a corner into the very first vertical plane as shown by thearrow, where the filament may be tied off 608 with the tail knot toprevent from slipping through tissue, although the filament may beknotted and a knot tied with an adjacent portion of the filament. Thus,the filament defines all four vertical walls of the cavity as well asthe approximate height of each wall along with the bottom of the cavityso that all six surgical planes will be visible under x-ray or otherimaging. Again, this shows a single continuous path but the path may bebroken down to multiple segments with multiple knots. Linear sectionsalong a plane are coupled together between planes with a connectorfilament which may be a right angled corner, or any shaped connector.Additionally, as previously discussed, FIG. 6 shows the filament visiblebut one of skill in the art will appreciate that the filament is suturedinto the tissue and therefore will have sections that are visible whileother sections will be invisible to the naked eye since they areembedded in tissue, but under an x-ray will show up as a continuousline.

The filaments may be attached to a plurality of the surfaces, includingmore than one surface in any example. In this example the filament maybe threaded in and out of the tissue, however, it can also be attachedto the walls of the tissue cavity with absorbable or non-absorbableclips, or any other attachment means. The clips may be radiopaque andthey can have certain markings to mark which plane they are attached, toprovide differentiation amongst the various surgical planes to thedoctor when the cavity is closed and viewed under x-ray, CT or otherimaging schemes. The clips can also be only ultrasound visible where themarker can be only x-ray/CT visible.

The next method is illustrated in FIG. 7, where contouring the cavity702 with a radiopaque marker 708 which may be any of those disclosedherein, includes starting 704 on one of the vertical planes (leaving afilament tail to eventually tie off to) and running a continuous ordiscontinuous loop threading through all four adjacent planes as well asa plane in the bottom of the cavity. First, the marker starts 704 in awall of the cavity in a vertical plane and extends a short lineardistance horizontally until it passes into the adjacent vertical planeand extends along the second vertical plane in a horizontal linearcontinuous path. The filament (also referred to herein as the radiopaquemarker or marker) then passes into into a third wall or third verticalplane and extends along that plane in horizontal manner until it passesinto the fourth vertical plane, again in a continuous or discontinuouspath then back into the original first vertical plane. The filament mayextend partially along the first vertical plane up to but not past thestarting point 704 where it may be sutured 706 to the tail at the start704, or it may extend anywhere before, after or to the starting point704 forming a loop. Also, the filament at the start 704 may be knottedto provide an anchor either alone or in conjunction with being tied tothe tail. The loop may be in a plane that is parallel or transverse tothe bottom of the cavity. Once the marker extends at least partiallylong the first vertical plane in a horizontal manner, the marker thenturns downward to extend down the first vertical plan in a linear pathuntil it hits the bottom of the cavity in the bottom plane or adjacentto it. Again this may be a continuous or discontinuous path. When themarker hits the bottom plane or is adjacent the bottom plane, the markerthen turns directions again and passes along the bottom of the cavity inthe bottom plane in a continuous or discontinuous manner and in a linearpath to cross the bottom of the cavity until the marker comes to thethird vertical plane where the marker then turns and extends upwardly inthat plane and it may or may not cross over the the first horizontalsegment in that plane. The marker then turns and extends horizontallyalong the third plane, crosses into the fourth vertical plane andextends across the fourth vertical plane in a continuous ordiscontinuous linear path and then turns again into the first verticalplane where the marker extends in a linear continuous or discontinuouspath horizontally toward the start 704 and the tail and marker may betied together. Thus, the marker extends through the perimeters of thecavity allowing a physician to visualize the cavity under x-ray lateron.

As previously mentioned, the entire path can be done in multiplesegments with multiple knots joining the segments instead of just asingle continuous segment and single knot. The filament can bethreaded/sutured into and out of the tissue, or attached via mechanicalmeans like clips.

FIG. 8 show an example where two filaments (or markers) which may be anyof those disclosed herein are used to outline two two horizontal planesin a surgical cavity 802 or other cavity. The technique uses two loops,one on the posterior plane and one on the anterior plane, or any othertwo planes such as a medial and lateral plane, or a superior andinferior plane. First, the filament starts 804 on a wall of the cavityin a vertical plane, extends horizontally along that plane, turns intoan adjacent cavity wall and vertical plane, extends horizontally alongthe second vertical plane until it turns again into a third cavity walland third vertical plane. The marker extends linearly and horizontallyalong the third vertical wall until it turns and extends horizontallyalong the fourth cavity wall or fourth plane. The marker extendslinearly and horizontally along the fourth plane and then turns andcrosses back into the first plane where the end of the filament is tied806 with a tail of the filament at the start 804. Here the filament iscontinuous around the cavity perimeter but it may be discontinuous.Additionally, the marker forms a loop around the perimeter and loop maybe in a plane that is parallel or transverse to the plane of the bottomof the cavity.

Similarly, a second loop is formed below the first loop. The markerstarts 808 and extends around the cavity perimeter and through all thevertical planes defining the walls of the cavity until the marker istied 810 off with the filament at the start 808, substantially similarlyas described with respect to the first loop. The two loops may lie inplanes that are parallel to one another, or transverse to one another.The loops may lie in planes that are parallel or transverse to thebottom of the cavity. Also, the loops may be continuous loops or theymay be formed discontinuously by multiple segments disposed around theperimeter. A segment may be disposed in one plane, two planes, threeplanes, four planes, five planes, six planes, or more than six planes.

The loops may be placed anywhere along the cavity but in one example theloops are disposed as close to the top and as close to the bottom of thecavity so that the surgeon can easily determine the depth of the cavity.Using two loops also delineates all six surgical planes. The filamentmay be threaded, clipped, or otherwise attached to the tissue.

FIG. 9 shows another example that uses two separate filaments to mark acavity 902. The first filament generally takes the same form as any oneof the loops in FIG. 8 above. Here, the marker starts 904 horizontallyextending across a first vertical plane until it crosses over into thesecond vertical plane and extends horizontally across the secondvertical plane until crossing into the third vertical plane which may beopposite to the first vertical plane. The marker extends horizontallyalong the third vertical plane until it crosses into the fourth verticalplane, extends horizontally along the fourth vertical plane and thencrosses back into the first vertical. It extends horizontally along thefirst vertical plane until it reaches a tail at the starting point 904and the two ends can then be knotted together to form a closed loop. Theloop may be formed by a continuous linear path. The ends may not beknotted together and thus an open loop may also be formed. The loop maybe parallel or transverse to the plane of the bottom of the cavity andallows easy visualization of the top of the cavity which may be theanterior surgical plane.

A second marker starts 908 in the first vertical plane, just inferior tothe knot 906 and extends linearly downward along the first verticalplane until it crosses into the bottom cavity plane and extends linearlyalong the bottom cavity plane. The marker continues across the bottomcavity plane until it crosses into the third vertical plane opposite thefirst vertical plane. The marker extends upward linearly along the thirdvertical plane and may stop 910 either inferior to or superior to thefirst loop. The ends of the filament are not knotted together. Thesecond partial loop may be orthogonal to the first loop or transversethereto and further facilitates identification of the two verticalplanes and the bottom of the cavity which may be the posterior plane.

In either loop of FIG. 9, the marker may be sutured into tissue orotherwise attached to the tissue such as with clips or other techniquesknown in the art. Similarly, the example of FIG. 9 shows that the twoloops are formed with a continuous linear filament but this may also beformed with discontinuous segments. Also this marker pattern allows aphysician to visualize the height of the tumor bed and identifies theposterior plane. The start 908 of the second loop may be coupled to thefirst loop and also optionally the end 910 of the second loop may alsobe attached to the first loop by knotting them together, clipping orusing other attachment techniques.

Another pattern could be created by simply crossing the planes as seenin FIG. 10. In this example the radiopaque marker or filament may start1002 in one upper portion of a vertical plane and extend horizontallyacross that plane in a linear path until the filament crosses into anadjacent vertical plane. The filament then curves downward and extendsin a diagonal linear path 1004 across the second vertical plane towardthe bottom of the cavity where the filament then turns into a thirdvertical plane and passes linearly and horizontally 1005 across thebottom of the third vertical plane adjacent the bottom of the cavityuntil reaching a fourth vertical plane. The filament extends upwardlyand linearly in a diagonal path 1006 from the bottom of the cavity inthe fourth vertical plane and crosses to an opposite upper region of thefourth vertical plane adjacent where the filament started in the firstvertical plane. The two filament ends may then be knotted 1008 togetherforming a closed square or rectangular loop that is canted in thecavity. Similarly, a second square or rectangular loop may be formed inthe cavity. The second loop starts 1010 with a filament in an upperportion of the third vertical plane (opposite the first vertical plane)and extends linearly and horizontally along the third vertical planeuntil crossing into the second vertical plane where is then turns andextends diagonally downward 1012 to the opposite side of the secondvertical plane near the bottom of the cavity. The filament turns againinto the first vertical plane and extends linearly and horizontally 1014across the bottom of the first vertical plane until reaching the fourthvertical plane where the filament then extends vertically and diagonally1016 across the fourth vertical plane until ending adjacent the startingpoint where the two ends may be knotted 1018 together to form the closedloop. The two loops therefore form an “X” pattern in the cavity andhighlight the walls of the cavity, and the upper and lower locations ofthe cavity. This also creates a plane that is angled from the anteriorto posterior surfaces. The pattern may also be produced using segmentsof markers disposed on the same path.

As mentioned earlier, an oncoplastic lumpectomy surgically brings tissueplanes together to eliminate the physical void created when breast tumortissue (“lump”) is removed. It should be appreciated that when thecavity is closed, the previously attached filament can move with thetissue as the tissue is moved inward or during normal tissue movement.Unlike rigid markers mentioned earlier that are not deformable as thecavity moves, examples of the filament described herein move with thecavity. Described below are examples showing how opposing walls arebrought in/re-approximated. This shows how two opposing walls arebrought in, however it is possible that all four walls are moved atdifferent heights to fill in the void left by the tumor tissue. Althoughthe walls are moved, the originally placed marker can move with thewalls.

FIG. 7 depicts how the marker is originally attached to the walls of acavity and FIG. 11 shows how the marker deforms with the tissue wallswhen they are apposed with one another. In FIG. 11, markers 1102 inopposite vertical planes are pulled in toward one another as the tissuein those walls are apposed with one another to close the cavity. Themarker position of the other filaments remain substantially the same asoriginally described in FIG. 7 since there is substantially no othertissue movement. The filament now outlines the tumor bed once the tissueplanes have been moved.

FIG. 11 may be idealized but does emphasize that the center portion ofopposing walls move inward toward one another while the outer portionsof opposing walls may move inward less and thus there is correspondingmovement of the marker.

As demonstrated, the filament represents the delineated marginsregardless of surgical procedure performed after tumor excision andmarking of the tumor bed with the filament.

FIG. 11 and FIG. 7 represent the same marked tumor bed. FIG. 7 is theradiographic depiction with no tissue re-approximation after tumorexcision and filament placement. FIG. 11 is a radiographic example oftissue re-approximation or oncoplastic surgery after tumor excision andfilament placement. As mentioned earlier this only shows two walls beingmoved, however this can be done with all walls. Here the filament pathfollows any movement of the tissue planes. FIG. 12 shows another examplehow the filament outlines the moved tissue.

FIG. 8 shows the tumor bed prior to tissue movement and after tissuemovement in FIG. 12. As can be seen in FIG. 12, the opposite planes weremoved and the filament outlines the path 1202 of the moved tissuecompared to the original path as depicted in the original FIG. 8. Again,the filament follows the path of the tissue that is moved.

It is feasable that the physician or surgeon can leave some slack whenthe filament is attached to the tissue in any of the examples,especially when the tissue has to be moved so that the filament canfollow the new path. The filament can also be pulled to close the tissuetogether and act as a suture. So if the filament is brought around thetumor bed, it may be pulled up and cinched so the cavity closed.

In yet another example, as seen in FIG. 13, a new pattern can beconstructed, similar the spiral shown earlier in FIG. 4. The differenceis creating a small knot 1302 at the proximal end of the marker. In thisexample the proximal knot 1302 is used to anchor the marker at one ofthe surgical planes (anterior, posterior, lateral, medial, superior orinferior). In this example it is the posterior plane (where the top ofthe box represents the anterior plane). Here, the maker is inserted intotissue and pulled through all the way out until the knot prevents anyfurther movement. This will anchor the proximal end of the marker andfrom here any of the patterns can be initiated. The knot is large enoughso it does not slip through the tissue, especially when passing throughfatty tissue. In this example, the surgeon starts the marker in thebottom of the cavity which here is the posterior plane by anchoring themarker with knot 1302. From there, the filament outlines the posteriorplane by passing the marker continuously in an upwardly sloping linearpath around the lateral, medial, superior and inferior planes (verticalplanes) and once the surgeon is satisfied with the outline, the surgeonwill begin to angle the marker towards the anterior plane and continueto traverse around all planes mentioned in an upward spiral 1304. In anyof the examples disclosed herein where a tail of the filament is tiedwith another portion of the filament, this may be substituted with asimple knot in the filament that prevents the filament from passingthrough the tissue and without forming a knot with another portion ofthe filament.

Once the desired height is reached, instead of closing the loop asdemonstrated in previous patterns and tying the loop off, a simple knot1306 can be made on the distal end of the marker to prevent it frombeing pulled back. So, this example describes a proximal anchor anddistal anchor. These anchors are described as just knots, howevermechanical means, like clips can be used to stake the ends onto tissue.As mentioned earlier, in this or any example, the filament may be tiedwith another portion of the filament, or a single or multiple knots canbe deployed to ensure that the filament does not slip through thetissue.

The previous examples described above have assumed that markers areplaced between the anterior and posterior planes as seen in all thepatterns shown, however this is not intended to be limiting. Definingthe surgical cavity starts at the anterior plane and extends down to theposterior plane. It is entirely possible that the cavity starts at thelateral plane 1404 and extends to the medial plane as seen in FIG. 14which also shows the anterior plane 1402 and the posterior plane 1406.So, all the patterns can be repeated, except that the pattern will berotated to show where the access plane is, for example lateral in FIG.14. Therefore, one of skill in the art will appreciate that themarker(s) may start, end or otherwise be placed in any plane and hencethe examples are not limited to specific planes.

One advantage of a continuous radiopaque marker filament is that it canbe used as a suture to bring and hold tissue together as illustrated inFIG. 15. This is helpful when internal structures are brought together.The marker can be imaged and thus show how well the closure has held up.So post-operative images can be taken over time to see if the marker hasnow changed in shape (deformed) thus depicting how well the tissue hasre-approximated and stayed together.

FIG. 15 shows to ends of tissue 1502, 1504 which are apposed with oneanother and then sutured 1506 together. The suture may be any of theexamples of radiopaque sutures or markers disclosed herein. The suturewill then be visible under x-ray.

Also, markers may be used to identify tissue or used as targets forexternal beam irradiation. Another value of the marker is that it can beused with internal radiation technologies such as brachytherapy. Sincethe cavity is not filled with a marker and only the outline is marked,surgical catheters that deliver internal radiation such as acceleratedpartial breast radiation can be used in conjunction with the continuousradiopaque marker. A pattern, similar to FIG. 6 can be deployed forexample with a brachytherapy insertion, where the anterior plane opensup to deliver the brachytherapy catheter. Any filament or marker may beused in any example of a pattern with or without brachytherapy.

FIG. 16 shows another example where applying the markers disclosedherein may be applied to other anatomical structures. Rather thandelineating the tumor bed with filament threads inside the bed, thismethod illustrates the concept of using loops or segments of filamentthread 1602 to mark the site of an anastomosis 1604 following removal ofdiseased tissue along a tubular or longitudinal structure where anopening is created when disease intervening along such a structure issurgically removed. The open ends 1606, 1608 are surgically reconnectedwith sutures or similar methods, thereby creating the anastomosis 1604.Here the filament marker 1602 is applied to one or more sides around theanastomosis. In this example the marker is circumferentially disposedaround all or a portion of the perimeter of both ends of tissue joinedtogether.

Common examples where anastomoses are formed include a colorectalanastomosis, esophagogastric anastomosis, and bronchial anastomosisafter lung resection. After surgery, an anastomosis is difficult to seewith x-ray based imaging techniques routinely used to plan and targetradiation therapy around the anastomosis which presents a challengesince the anastomosis is the area at highest risk of recurrence ofdisease. However, intraoperative placement of filament threads on eitherside of the anastomosis will permit the radiation oncologist tosubsequently delineate the site of anastomosis that requires radiationtherapy. Beyond providing the precise location of the anastomosis, thesurgeon can also place the filament thread(s) in a location that willassist the radiation oncologist in other ways to better designpostoperative radiation therapy. For example, based upon observationsthat can be made only intraoperatively, the surgeon can elect to place aloop or segment of filament thread to mark an area that should notreceive a higher dose of radiation therapy than necessary (e.g.,location of a critical blood supply, delicate watershed area,compromised tissue, etc.). For a small area that would benefit fromvisual delineation to guide postoperative therapy, a knot of filamentthread would suffice. As seen in this figure a small knot is formed withthe marker next to a critical structure to highlight it under imaging.The applications for using this technique can also be applied tovessels, nerves etc. The concept is to mark the area of interventionsuch as anastomosis for follow-up imaging. When vessels are connected,there may be interest to know the location of that anastomosis with orwithout radiation therapy.

FIG. 17 shows a region of tissue 1702 being treated and having sensitivetissue or an area 1704 that the physician desires to mark with a marker1706 so that it is visible later under x-ray. That way the marked tissuemay be easily identified and excluded from irradiation or othertreatments later. Examples of sensitive tissue 1704 include but are notlimited to those disclosed above including vessels or nerves. Any markerdisclosed herein may be used as the marker 1706 in this example,

In some examples, a series of discrete markers may be used to outlinethe target area. The discrete markers may be short segments of theradiopaque suture filaments described herein and separated by a gap. Ora plurality of discrete radiopaque markers separated by a gap may bedisposed on a continuous suture filament. The gap or distance betweenradiopaque markers may be equal to or less than the distance or lengthof the marker portions which helps form a substantially continuous lineunder x-ray so that the physician does not have to extrapolate where thetarget area boundaries are.

In sonic examples, the marker may be integrated into a material. Thematerial may be injected or placed into a desired location as long asthe material is transparent to the imaging modalities. The material maybe three dimensional to fill a cavity. The marker should not obstructimaging.

In any example, the radiopaque marker permits unambiguousthree-dimensional visualization of the site of interest which may be atumor bed. Visualization is achieved without requiring extrapolation orinterpretation of the site borders. This is contrary to traditionalmarkers such as clips which do require an observer to extrapolate a lineor surface between discrete points. Moreover, examples of the currentmarker do not migrate once placed in the tissue unlike clips and othermarkers which can move and therefore distort visualization of the siteof interest.

Some examples, the marker may be placed in the site of interest to forma lattice or mesh which allows the site to be visualized. In otherexamples, the marker may be placed continuously or with a plurality ofdiscrete markers so that the marker is coaxial along its length. Inother examples, the marker may be placed such that three points areplaced in one surgical plane to help the observer visualize the firstsurgical plane, and the marker may also be placed in a second or anynumber of additional surgical planes with at least three points in eachsurgical plane to allow the observer to clearly visualize each surgicalplane. The marker may be placed in the any of the permutations orcombinations of the following surgical planes including the anterior,posterior, lateral, medial, superior and inferior planes.

In any example, the length of the marker may be >0.5 mm, >1 mm, >2mm, >3 mm, >4 mm, >5 mm, >6 mm, >7 mm, >8 mm, >9 mm, >10 mm, >11 mm, >12mm, >13 mm, >14 mm, >15 mm, >16 mm, >17 mm, >18 mm, >19 mm, >20 mm, >21mm, >22 mm, >23 mm, >24 mm, >25 mm, >26 mm, >27 mm, >28 mm, >29 mm, >30mm, >31 mm, >32 mm, >33 mm, >34 mm, >35 mm, >36 mm, >37 mm, >38 mm, >39mm, >40 mm, >41 mm, >42 mm, >43 mm, >44 mm, >45 mm, >46 mm, >47 mm, >48mm, >49 mm, or >50 mm.

In any example where there are gaps between markers, the gap distancemay be <50 mm, <49 mm, <48 mm, <47 mm, <46 mm, <45 mm, <44 mm, <43 mm,<43 mm, <42 mm, <41 mm, <40 mm, <39 mm, <38 mm, <37 mm, <36 mm, <35 mm,<34 mm, <33 mm, <32 mm, <31 mm, <30 mm, <29 mm, <28 mm, <27 mm, <26 mm,<25 mm, <24 mm, <23 mm, <22 mm, <21 mm, <20 mm, <19 mm, <18 mm, <17 mm,<16 mm, 15 mm, <14 mm, <13 mm, <12 mm, <11 mm, <10 mm, <9 mm, <8 mm, <7mm, <6 mm, <5 mm, <4 mm, <3 mm, <2 mm, <1 mm, <0.05 mm. In all caseswhere there is a gap, the gap must be greater than 0 mm.

Any example of a marker may include a solid core and yet still be aflexible marker that is radiopaque. The flexibility should be adequateto allow the marker to conform to the site of interest with symmetric ornon-symmetric shape area or volume and also allow the marker to be tiedinto a knot. The marker encloses the area or volume to allow thephysician to determine the treatment plan or region without requiringextrapolation of the area or volume based on the markers.

Any example may be a radiopaque, flexible marker that can be implantedpermanently and attached, sutured or otherwise coupled to tissue. Anyexample may be a flexible, continuous, radiopaque, implantable markerthat once deployed in tissue allows measurement of the area or thevolume. The marker may have any of the characteristics of the markersdisclosed in U.S. patent application Ser. No. 16/160,229 previouslyincorporated herein by reference. Any marker disclosed herein may haveuniform radiopacity characteristics, or one side of the marker may havedifferent radiopacity characteristics relative to a second side of themarker. Any marker disclosed herein may be formed into a spring elementthat can expand from a collapsed configuration to fill a void orsurgical or other cavity.

While the devices and methods disclosed herein have primarily beendisclosed with reference to use in living human tissue, one of skill inthe art will appreciate that this is not intended to be limiting. Thedevices and methods disclosed herein may be used in animals, cadavertissue, or other non-tissue materials. For example, a synthetic graftmay use any of the devices and methods disclosed herein to mark thedevice prior to use. Similarly, a stent-graft or prosthetic valve havinga cover and expandable frame may be assembled before implantation usingradiopaque filaments to secure the cover to the expandable frame. Also,the devices and methods disclosed herein may be used on fabric orsynthetic materials for training, demonstration, assembly, or othernon-treatment purposes. In all the previous examples, the application ofthe marker may be performed in open surgery, laparoscopic surgery andeven percutaneous surgery. Having the filament delivered through alaparoscopic cannula for example, such as in a standard or roboticapplication is entirely feasible. For example, a needle may be used thatis small enough to fit through the cannula and then deployed usingstandard laparoscopic instruments.

Any of the examples of radiopaque markers may be used as part of systemwhich may include other surgical instruments, radiotherapy treatmentsupplies such as brachytherapy, radiotherapy planning software, tumorlocalization solutions, tumor radiographic imaging, or other items.Examples of tumor localization solutions including wires, as well asmagnetic and radiofrequency based equipment. Examples of tumorradiographic imaging equipment include x-ray, ultrasound, CT, andmammography equipment.

FIG. 20 illustrates an example of a radiopaque marker 2000 which may beany of the examples disclosed herein with anchors 2002 which may becoupled to the radiopaque marker in order to prevent movement of themarker once coupled to the tissue. The anchors 2002 may be placed at oneend of the radiopaque marker, on both ends, in a middle portion,combinations thereof, or in any position along the marker. Examples ofanchors may be clips, barbs, or any of the other anchor elementsdisclosed herein.

NOTES AND EXAMPLES

The following, non-limiting examples, detail certain aspects of thepresent subject matter to solve the challenges and provide the benefitsdiscussed herein, among others.

Example 1 is a method for marking a target with a radiopaque marker,said method comprising: providing a radiopaque filament; inserting atleast a portion of the radiopaque filament into tissue; extending theradiopaque filament continuously at least partially around a perimeterof the target and disposing the radiopaque filament in a plurality ofsurgical planes, thereby demarcating the target with the radiopaquemarker.

Example 2 is the method of Example 1, further comprising disposing atleast a portion of the radiopaque filament adjacent an outer surface ofthe tissue so that the portion of the radiopaque filament is uncoveredby the tissue.

Example 3 is the method of any of Examples 1-2, wherein extending theradiopaque filament comprises continuously following a contour of acavity with the radiopaque filament.

Example 4 is the method of any of Examples 1-3, further comprisingforming one or more knots in the radiopaque filament.

Example 5 is the method of any of Examples 1-4, wherein the plurality ofsurgical planes comprises at least two or more of a superior plane,inferior plane, lateral plane, medial plane, anterior plane, and aposterior plane.

Example 6 is the method of any of Examples 1-5, wherein at least some ofthe plurality of planes are parallel to one another.

Example 7 is the method of any of Examples 1-6, wherein at least some ofthe plurality of planes are transverse or orthogonal to one another.

Example 8 is the method of any of Examples 1-7, wherein the radiopaquefilament extends between the plurality of planes.

Example 9 is the method of any of Examples 1-8, wherein walls of thecavity form a tubular structure, and wherein the radiopaque filamentextends at least partially circumferentially around the tubularstructure.

Example 10 is the method of any of Examples 1-9, wherein the radiopaquefilament forms a continuous line in the tissue.

Example 11 is the method of any of Examples 1-10, wherein the radiopaquefilament forms a closed loop in the tissue.

Example 12 is the method of any of Examples 1-11, wherein the radiopaquefilament demarcates a rectangular region or a conical region in thetissue.

Example 13 is the method of any of Examples 1-12, wherein the radiopaquefilament demarcates a region of malignant, diseased or damaged tissuethat has been excised from a patient.

Example 14 is the method of any of Examples 1-13, wherein extending theradiopaque filament comprises disposing the radiopaque filament in aspiral pattern in the tissue.

Example 15 is the method of any of Examples 1-14, further comprisinginhibiting movement of the radiopaque filament relative to the tissuewith barbs or one or more knots, disposed on the radiopaque filament,the barbs or one or more knots configured to engage with the tissue.

Example 16 is the method of any of Examples 1-15, further comprisinginhibiting movement of the radiopaque filament with a coating disposedthereon that resists slidable movement of the radiopaque filamentrelative to the tissue.

Example 17 is the method of any of Examples 1-16, further comprisingobserving the radiopaque filament with radiographic imaging.

Example 18 is the method of any of Examples 1-17, wherein the radiopaquefilament further comprises an echogenic coating or pattern disposedthereon, the method further comprising visualizing the radiopaquefilament with ultrasound.

Example 19 is the method of any of Examples 1-18, wherein a first sideof the radiopaque filament has a first radiopacity and isdistinguishable from a second side of the radiopaque filament which hasa second radiopacity, as viewed under radiographic imaging.

Example 20 is the method of any of Examples 1-19, wherein the radiopaquefilament forms a spring element.

Example 21 is the method of any of Examples 1-20, wherein the radiopaquefilament forms an expandable radiopaque marker configured to expand andfill a void left by excision of malignant, diseased or damaged tissue.

Example 22 is the method of any of Examples 1-21, wherein the radiopaquefilament comprises a proximal end and a distal end, the method furthercomprising anchoring the proximal or distal end to tissue by knottingthe proximal or distal end of the radiopaque filament.

Example 23 is the method of any of Examples 1-22, wherein both theproximal and distal ends are anchored to the tissue.

Example 24 is the method of any of Examples 1-23, wherein inserting atleast a portion of the radiopaque filament into tissue comprisesstarting deployment of the radiopaque filament in an anterior plane andmoving the radiopaque filament toward a posterior plane.

Example 25 is the method of any of Examples 1-24, wherein inserting atleast a portion of the radiopaque filament into tissue comprisesstarting deployment of the radiopaque filament in in a lateral plane andmoving the radiopaque filament toward a medial plane.

Example 26 is the method of any of Examples 1-25, further comprisingtensioning the radiopaque filament thereby apposing the tissue.

Example 27 is the method of any of Examples 1-26, further comprisingapplying brachytherapy to the target.

Example 28 is a radiopaque marker comprising: an elongate flexibleradiopaque filament visible under radiographic imaging, and wherein theradiopaque marker is disposed continuously in one or a plurality ofsurgical planes.

Example 29 is the radiopaque marker of Example 28, wherein theradiopaque marker extends between the plurality of planes.

Example 30 is the radiopaque marker of any of Examples 28-29, whereinthe radiopaque marker is disposed in a plurality of continuous linesinterconnected with arcuate connections therebetween.

Example 31 is the radiopaque marker of any of Examples 28-30, whereinthe radiopaque marker comprises 20% to 40% by weight of the radiopaquematerial.

Example 32 is the radiopaque marker of any of Examples 28-31, whereinthe elongate flexible filament has a diameter ranging from 0.1mm to0.3mm.

Example 33 is the radiopaque marker of any of Examples 28-32, whereinthe elongate flexible filament has a circular cross-section.

Example 34 is the radiopaque marker of any of Examples 28-33, whereinthe elongate flexible filament has a diameter larger than 0.4 mm.

Example 35 is the radiopaque marker of any of Examples 28-34, whereinthe elongate flexible filament has a diameter larger than 1mm.

Example 36 is the radiopaque marker of any of Examples 28-35, whereinthe elongate flexible filament has a tensile strength between 5 and 20Newtons.

Example 37 is the radiopaque marker of any of Examples 28-36, whereinthe elongate flexible filament has an elongation greater than 50%.

Example 38 is the radiopaque marker of any of Examples 28-37, whereinthe radiopaque filament comprises barium sulfate.

Example 39 is the radiopaque marker of any of Examples 28-38, furthercomprising a coating on the elongate filament, the coating configured toincrease friction of the elongate filament passing through tissue.

Example 40 is the radiopaque marker of any of Examples 28-39, whereinthe elongate filament is formed into a closed loop.

Example 41 is the radiopaque marker of any of Examples 28-40, whereinthe elongate filament is formed into a spiral.

Example 42 is the radiopaque marker of any of Examples 28-41, whereinthe elongate filament is knotted in one or more regions.

Example 43 is the radiopaque marker of any of Examples 28-42, whereinthe elongate filament comprises a plurality of segments, each segmentdisposed in different planes.

Example 44 is the radiopaque marker of any of Examples 28-43, whereinthe plurality of surgical planes comprises at least two or more of asuperior plane, inferior plane, lateral plane, medial plane, anteriorplane, and a posterior plane.

Example 45 is the radiopaque marker of any of Examples 28-44, whereinthe elongate filament comprises a proximal end and a distal end, theelongate filament further comprising an anchor element disposed adjacentthe proximal or distal end.

Example 46 is the radiopaque marker of any of Examples 28-45, whereinthe anchor element comprises a knot.

Example 47 is the radiopaque marker of any of Examples 28-46, wherein afirst end of the elongate filament is configured to be disposed in ananterior plane of a patient and the elongate filament extends toward aposterior plane of the patient.

Example 48 is the radiopaque marker of any of Examples 28-47, wherein afirst end of the elongate filament is configured to be disposed in alateral plane of a patient and the elongate filament extends toward amedial plane of the patient.

Example 49 is the radiopaque marker of any of Examples 28-48, whereinthe elongate filament is configured to be disposed in tissue, andwherein the elongate filament is configured to be drawn to itself whentension is applied thereto, thereby apposing the tissue.

Example 50 is a system for treating a patient, comprising the radiopaquemarker of any of Examples 28-49; and one or more brachytherapyirradiation elements.

Example 51 is a radiopaque marker comprising a plurality of radiopaquesegments coupled to a filament with gaps disposed between adjacentradiopaque segments, wherein the gap is <50 mm.

Example 52 is a radiopaque marker comprising a plurality of radiopaquesegments disposed in a plurality of planes, wherein the plurality ofsegments are coaxial with one another.

Example 53 is a radiopaque marker, comprising a plurality of radiopaquesegments disposed in a plurality of planes forming a lattice or mesh ofradiopaque segments allowing visualization of a target region withoutextrapolation of the plurality of radiopaque segments.

Example 54 is a radiopaque marker comprising at least three radiopaquesegments disposed in a first plane and at least three radiopaquesegments disposed in a second plane.

Example 55 is a radiopaque marker comprising a marker element having asolid core that is flexible and radiopaque, wherein the marker elementis flexible enough to allow a knot to be tied therewith.

Example 56 is a radiopaque marker comprising a flexible radiopaqueelement which can be deployed into symmetric or non-symmetric shapes,areas, or volume and into at least a single plane.

Example 57 is a method for marking a target with a radiopaque marker,comprising providing a radiopaque filament; inserting at least a portionof the radiopaque filament into a non-living material; and extending theradiopaque filament continuously at least partially around a perimeterof the target and disposing the radiopaque filament in a plurality ofplanes, thereby demarcating the target with the radiopaque marker.

In Example 58, the devices, systems or methods of any one or anycombination of Examples 1-57 can optionally be configured such that allelements or options recited are available to use or select from.

The above detailed description includes references to the accompanyingdrawings, which form a part of the detailed description. The drawingsshow, by way of illustration, specific embodiments in which theinvention can be practiced. These embodiments are also referred toherein as “examples.” Such examples can include elements in addition tothose shown or described. However, the present inventors alsocontemplate examples in which only those elements shown or described areprovided. Moreover, the present inventors also contemplate examplesusing any combination or permutation of those elements shown ordescribed (or one or more aspects thereof), either with respect to aparticular example (or one or more aspects thereof), or with respect toother examples (or one or more aspects thereof) shown or describedherein.

In the event of inconsistent usages between this document and anydocuments so incorporated by reference, the usage in this documentcontrols.

In this document, the terms “a” or “an” are used, as is common in patentdocuments, to include one or more than one, independent of any otherinstances or usages of “at least one” or “one or more.” In thisdocument, the term “or” is used to refer to a nonexclusive or, such that“A or B” includes “A but not B,” “B but not A,” and “A and B,” unlessotherwise indicated. In this document, the terms “including” and “inwhich” are used as the plain-English equivalents of the respective terms“comprising” and “wherein.” Also, in the following claims, the terms“including” and “comprising” are open-ended, that is, a system, device,article, composition, formulation, or process that includes elements inaddition to those listed after such a term in a claim are still deemedto fall within the scope of that claim. Moreover, in the followingclaims, the terms “first,” “second,” and “third,” etc. are used merelyas labels, and are not intended to impose numerical requirements ontheir objects. The above description is intended to be illustrative, andnot restrictive. For example, the above-described examples (or one ormore aspects thereof) may be used in combination with each other. Otherembodiments can be used, such as by one of ordinary skill in the artupon reviewing the above description. The Abstract is provided to allowthe reader to quickly ascertain the nature of the technical disclosure.It is submitted with the understanding that it will not be used tointerpret or limit the scope or meaning of the claims. Also, in theabove Detailed Description, various features may be grouped together tostreamline the disclosure. This should not be interpreted as intendingthat an unclaimed disclosed feature is essential to any claim. Rather,inventive subject matter may lie in less than all features of aparticular disclosed embodiment. Thus, the following claims are herebyincorporated into the Detailed Description as examples or embodiments,with each claim standing on its own as a separate embodiment, and it iscontemplated that such embodiments can be combined with each other invarious combinations or permutations. The scope of the invention shouldbe determined with reference to the appended claims, along with the fullscope of equivalents to which such claims are entitled.

The invention claimed is:
 1. A method for marking a target with aradiopaque marker, said method comprising: providing a radiopaquefilament; weaving the radiopaque filament into and out of tissue; andextending the radiopaque filament continuously at least partially arounda perimeter of the target and extending the radiopaque filament in aplurality of surgical planes and between the plurality of surgicalplanes, thereby demarcating the target with the radiopaque marker. 2.The method of claim 1, wherein extending the radiopaque filamentcomprises continuously following a contour of a cavity with theradiopaque filament.
 3. The method of claim 1, further comprisingforming one or more knots in the radiopaque filament.
 4. The method ofclaim 1, wherein the radiopaque filament forms a continuous line in thetissue.
 5. The method of claim 1, wherein the radiopaque filament formsa closed loop in the tissue.
 6. The method of claim 1, wherein theradiopaque filament demarcates a region of malignant, diseased ordamaged tissue that has been excised from a patient.
 7. The method ofclaim 1, wherein extending the radiopaque filament comprises disposingthe radiopaque filament in a spiral pattern in the tissue.
 8. The methodof claim 1, further comprising inhibiting movement of the radiopaquefilament relative to the tissue with one or more knots disposed on theradiopaque filament, the one or more knots configured to engage with thetissue.
 9. The method of claim 1, wherein the radiopaque filamentcomprises a proximal end and a distal end, the method further comprisinganchoring the proximal or distal end to tissue by knotting the proximalor distal end of the radiopaque filament.
 10. The method of claim 1,further comprising tensioning the radiopaque filament thereby apposingthe tissue.
 11. The method of claim 1, further comprising applyingbrachytherapy to the target.
 12. A radiopaque marker, said markercomprising: an elongate flexible radiopaque filament visible underradiographic imaging, wherein the radiopaque marker is disposedcontinuously in a plurality of surgical planes and between the pluralityof surgical planes, and wherein the elongate flexible radiopaquefilament is configured to be woven into and out of tissue to extend atleast partially around a perimeter of a cavity.
 13. The marker of claim12, wherein the radiopaque marker is disposed in a plurality ofcontinuous lines interconnected with arcuate connections therebetween.14. The marker of claim 12, wherein the elongate filament is formed intoa closed loop.
 15. The marker of claim 12, wherein the elongate filamentis formed into a spiral.
 16. The marker of claim 12, wherein theelongate filament is knotted in one or more regions.
 17. The marker ofclaim 12, wherein the elongate filament comprises one or more radiopaquesegments.
 18. A radiopaque marker, comprising: a flexible and radiopaqueelement which is configured to be deployed into symmetric ornon-symmetric patterns, areas, or volume and into at least a singlesurgical plane, and wherein the flexible and radiopaque element isconfigured to be woven into and out of tissue to extend at leastpartially around a perimeter of a cavity.
 19. The method of claim 1,wherein the radiopaque filament does not substantially fill the cavity.20. The method of claim 1, the radiopaque filament demarcates anon-symmetrical target.
 21. The method of claim 1, wherein theradiopaque filament comprises one or more radiopaque segments.
 22. Themarker of claim 12, wherein the elongate flexible radiopaque filament isconfigured to demarcate the cavity without substantially filling thecavity.
 23. The marker of claim 12, wherein the cavity is anon-symmetrical cavity, and wherein the elongate flexible radiopaquefilament is configured to demarcate the non-symmetrical cavity.
 24. Themarker of claim 18, wherein the flexible and radiopaque elementcomprises one or more radiopaque segments.